HBcAg (resides 1-183) has been expressed in E.coli were it assembles in the bacterial cytoplasm into icosahedral capsids. Deletion of the polybasic C-terminal 34 residues (protamine domain) produces assembly competent protein (residues 1- 149) which is suitable for structural analysis. The structure of the capsids has been previously determined by cryo-electron microscopy and by X-ray crystallography. The closely related HBeAg is a secreted soluble protein which is thought to modulate both the innate and adaptive immune responses so as to favor persistent or chronic infection as well being an important clinical marker. This protein is truncated at position 149 and in addition contains a 10 residue N-terminal extension derived from partial processing of precursor protein (residues (-10) to 149). The HBeAg-specific Fab e6, was found to form a stable complex with the recombinant produced HBeAg protein. The immune complex was crystallized and the structure of HBeAg was determined. The structure clarifies how the short N-terminal propeptide (10 residues), locked into place through formation of intramolecular disulfide bridges, induces a radically altered mode of dimerization relative to HBcAg (140 degree rotation). This modified structure precludes capsid assembly and forms a distinct antigenic repertoire, explaining why HBcAg and HBeAg are cross-reactive at the T-cell level (through sequence identity) but not at the B-cell level (through conformation). Previous structural determinations of nucleocapsid-antibody immune complexes by cryo-electron microscopy were performed with a panel of murine antibodies. This work has been extended to included human antibodies from clinical samples. The results indicate binding to distinct regions on the capsid surface (epitopes) which we had previously identified using the murine antibodies. New studies have focused on specific antibody binding to HBcAg capsids which may contribute to acute liver failure (ALF). The monoclonal antibody E1 Fab was generated from previous work (R.H. Purcell, NIAID) based on immunological and molecular biological studies of tissue from patients with ALF. The E1 Fab binds with high affinity to HBcAg core particles in a unique tangential manner. The binding orientation of the Fab to the HBcAg particles may cluster the membrane bound B-cell receptors, leading to the immunological crisis associated with ALF.